Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Anticancer potential of Marsdenia tenacissima extract: modulation of proliferation, apoptosis and SBEM gene expression in triple-negative breast cancer MDA-MB-231 cells
1Department of Oncology, The Affiliated Hospital of Guizhou Medical University, 550004 Guiyang, Guizhou, China
2Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, 550004 Guiyang, Guizhou, China
3Department of Oncology, Clinical Medical College, Guizhou Medical University, 550004 Guiyang, Guizhou, China
4Qingdao West Coast New Area People’s Hospital, 266000 Qingdao, Shandong, China
5The Third Affiliated Hospital of Guizhou Medical University, 550025 Guiyang, Guizhou, China
6The Second People’s Hospital of Yibin, 644000 Yibin, Sichuan, China
7The Second Affiliated Hospital of Guizhou Medical University, 550003 Kaili, Guizhou, China
DOI: 10.22514/ejgo.2024.115 Vol.45,Issue 6,December 2024 pp.40-47
Submitted: 22 February 2023 Accepted: 19 April 2023
Published: 15 December 2024
*Corresponding Author(s): Liang Liu E-mail: xuqing@stu.gmc.edu.cn
Marsdenia tenacissima (MT) is a herbal remedy that has been used for many years to treat cancer. While the anti-cancer properties of Marsdenia tenacissima extract (MTE) have been observed in several malignancies, its effect on the fundamental mechanisms of triple-negative breast cancer cells remains unclear. Here, we investigate the underlying anti-cancer mechanisms of MTE in MDA-MB-231 cells in regard to their proliferation, apoptosis, and the expression of the secretory breast epithelial mucin (SBEM) gene. Cell Counting Kit-8 (CCK-8) and Annexin V and propridium iodide (PI) staining kits were used to measure the proliferation and apoptosis in MDA-MB-231 cells, respectively. The effects of MTE on MDA-MB-231 cell migration were evaluated via scratch healing at 0 and 24 hours after treatment with different MTE concentrations. Western blot was used to detect the protein expressions of SBEM and apoptosis-related factors. Real-time quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect SBEM mRNA expression after different drug concentrations. CCK-8 assays indicated increased proliferation and inhibition of MDA-MB-231 cells with increasing MTE concentrations. Flow cytometry also showed a gradual dose-dependent increase in MDA-MB-231 cell apoptosis rate with increasing MTE concentrations. Additionally, MTE reduced the migration of MDA-MB-231 cells in a dose-dependent way. Proteomic experiments showed that the drug group downregulated the expression levels of B-cell Lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and SBEM in MDA-MB-231 cells, and RT-qPCR analysis showed that the expression of SBEM mRNA in MDA-MB-231 cells could be down-regulated in a dose-dependent manner by MTE. MTE exerted its anti-cancer effects on MDA-MB-231 cells by inhibiting their proliferation and migration, as well as inducing cell apoptosis. These effects might be associated with the down-regulation of BCL-2 and BCL-XL expression and the deregulation of SBEM mRNA expression.
Marsdenia tenacissima extract; MDA-MB-231; SBEM; Proliferation; Apoptosis
Qing Xu,Liang Liu,Mi Cao,Min Zhang,Qi-ying Chen. Anticancer potential of Marsdenia tenacissima extract: modulation of proliferation, apoptosis and SBEM gene expression in triple-negative breast cancer MDA-MB-231 cells. European Journal of Gynaecological Oncology. 2024. 45(6);40-47.
[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.
[2] Heer E, Harper A, Escandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. The Lancet Global Health. 2020; 8: e1027–e1037.
[3] Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, et al. Current and future burden of breast cancer: global statistics for 2020 and 2040. The Breast. 2022; 66: 15–23.
[4] Wang L, Zhou Y, Jiang L, Lu L, Dai T, Li A, et al. CircWAC induces chemotherapeutic resistance in triple-negative breast cancer by targeting miR-142, upregulating WWP1 and activating the PI3K/AKT pathway. Molecular Cancer. 2021; 20: 43.
[5] Garrido-Castro AC, Lin NU, Polyak K. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment. Cancer Discovery. 2019; 9: 176–198.
[6] Derakhshan F, Reis-Filho JS. Pathogenesis of triple-negative breast cancer. Annual Review of Pathology: Mechanisms of Disease. 2022; 17: 181–204.
[7] Jiang Y Z, Ma D, Suo C, Shi J, Xue M, Hu X, et al. Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies. Cancer Cell. 2019; 35: 428–440 e5.
[8] Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nature Reviews Clinical Oncology. 2016; 13: 674–690.
[9] Keenan TE, Tolaney SM. Role of immunotherapy in triple-negative breast cancer. Journal of the National Comprehensive Cancer Network. 2020; 18: 479–489.
[10] Wang X, Yan Y, Chen X, Zeng S, Qian L, Ren X, et al. The antitumor activities of Marsdenia tenacissima. Frontiers in Oncology. 2018; 8: 473.
[11] FAN W, SUN L, ZHOU J, ZHANG C, QIN S, TANG Y, et al. Marsdenia tenacissima extract induces G0/G1 cell cycle arrest in human esophageal carcinoma cells by inhibiting mitogen-activated protein kinase (MAPK) signaling pathway. Chinese Journal of Natural Medicines. 2015; 13: 428–437.
[12] To KKW, Wu X, Yin C, Chai S, Yao S, Kadioglu O, et al. Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes. Journal of Ethnopharmacology. 2017; 203: 110–119.
[13] Wang P, Yang J, Zhu Z, Zhang X. Marsdenia tenacissima: a review of traditional uses, phytochemistry and pharmacology. The American Journal of Chinese Medicine. 2018; 46: 1449–1480.
[14] Li H-T, Kang L-P, Guo B-L, Zhang ZL, Guan YH, Pang X, et al. Original plant identification of Dai nationality herb “Daibaijie”. China Journal of Chinese Materia Medica. 2014; 39: 1525–9. (In Chinese)
[15] Xie B, Jiang S, Shen X, Wu H, Hu Y. Pharmacokinetics, plasma protein binding, and metabolism of a potential natural chemosensitizer from Marsdenia tenacissima in rats. Journal of Ethnopharmacology. 2021; 281: 114544.
[16] Wu Z, Chen Y, Qu Z, Wu G, He X, Huang J, et al. An ester derivative of tenacigenin B from Marsdenia tenacissima (Roxb.) Wight et Arn reversed paclitaxel-induced MDR in vitro and in vivo by inhibiting both P-gp and MRP2. Journal of Ethnopharmacology. 2022; 294: 115353.
[17] Xie B, Lu Y, Luo Z, Qu Z, Zheng C, Huang X, et al. Tenacigenin B ester derivatives from Marsdenia tenacissima actively inhibited CYP3a4 and enhanced in vivo antitumor activity of paclitaxel. Journal of Ethnopharmacology. 2019; 235: 309–319.
[18] Zhang Y, Zhang Y. Marsdenia tenacissima extract inhibits proliferation and promotes apoptosis in human ovarian cancer cells. Medical Science Monitor. 2018; 24: 6289–6297.
[19] Wang K, Liu W, Xu Q, Gu C, Hu D. Tenacissoside G synergistically potentiates inhibitory effects of 5-fluorouracil to human colorectal cancer. Phytomedicine. 2021; 86: 153553.
[20] Hu Y, Liu P, Kang L, Li J, Li R, Liu T. Mechanism of Marsdenia tenacissima extract promoting apoptosis of lung cancer by regulating Ca2+/CaM/CaMK signaling. Journal of Ethnopharmacology. 2020; 251: 112535.
[21] Li S, Pei W, Yuan W, Yu D, Song H, Zhang H. Multi-omics joint analysis reveals the mechanism of action of the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Moon in the treatment of hepatocellular carcinoma. Journal of Ethnopharmacology. 2022; 293: 115285.
[22] Chen J, Zhang X, Xiao X, Ding Y, Zhang W, Shi M, et al. Xiao-Ai-Ping injection enhances effect of paclitaxel to suppress breast cancer proliferation and metastasis via activating transcription factor 3. Integrative Cancer Therapies. 2020; 19: 1534735420906463.
[23] Miksicek R J, Myal Y, Watson P H, Walker C, Murphy LC, Leygue E. Identification of a novel breast- and salivary gland-specific, mucin-like gene strongly expressed in normal and tumor human mammary epithelium. Cancer Research. 2002; 62: 2736–40.
[24] Gabellini C, Trisciuoglio D, Del Bufalo D. Non-canonical roles of Bcl-2 and Bcl-xL proteins: relevance of BH4 domain. Carcinogenesis. 2017; 38: 579–587.
[25] Sanaei M, Kavoosi F. Effect of Valproic Acid on the Class I histone deacetylase 1, 2 and 3, tumor suppressor genes p21WAF1/CIP1 and p53, and intrinsic mitochondrial apoptotic pathway, pro- (Bax, Bak, and Bim) and anti- (Bcl-2, Bcl-xL, and Mcl-1) apoptotic genes expression, cell viability, and apoptosis induction in hepatocellular carcinoma HepG2 cell line. Asian Pacific Journal of Cancer Prevention. 2021; 22: 89–95.
[26] Zhang J, Zhang S, Shi Q, Allen TD, You F, Yang D. The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells. Experimental Cell Research. 2020; 394: 112112.
[27] Lee E F, Harris T J, Tran S, Evangelista M, Arulananda S, John T, et al. BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival. Cell Death & Disease. 2019; 10: 342.
[28] Wang Y, Zhang Y, Guo Y, Lu J, Veeraraghavan VP, Mohan SK, et al. Synthesis of Zinc oxide nanoparticles from Marsdenia tenacissima inhibits the cell proliferation and induces apoptosis in laryngeal cancer cells (Hep-2). Journal of Photochemistry and Photobiology B: Biology. 2019; 201: 111624.
[28] Hao H, Tian W, Pan C, Jiao Y, Deng X, Fan J, et al. Marsdenia tenacissima extract dilated small mesenteric arteries via stimulating endothelial nitric oxide synthase and inhibiting calcium influx. Journal of Ethnopharmacology. 2019; 238: 111847.
[29] Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: an overview. International Journal of Cancer. 2021; 149: 778–789.
[30] Chen X, Luo Z, Liu X, et al. Marsdenia tenacissima (Roxb.) Moon injection exerts a potential anti-tumor effect in prostate cancer through inhibiting ErbB2-GSK3b-HIF1a signaling axis. Journal of Ethnopharmacology. 2022; 295: 115381.
[31] Jiao Y, Wu L, Xue D, Liu X, Tian Z, Jiang S, et al. Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells. Cancer Cell International. 2018; 18: 149.
[32] Zhou X, Liu M, Ren Q, Zhu W, Wang Y, Chen H, et al. Oral and injectable Marsdenia tenacissima extract (MTE) as adjuvant therapy to chemotherapy for gastric cancer: a systematic review. BMC Complementary and Alternative Medicine. 2019; 19: 366.
[33] Liu L, Liu Z, Qu S, Zheng Z, Liu Y, Xie X, et al. Small breast epithelial mucin tumor tissue expression is associated with increased risk of recurrence and death in triple-negative breast cancer patients. Diagnostic Pathology. 2013; 8: 71.
[34] Liu Z, Xie X, Qu S, Zheng Z, Wang Y. Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer. Clinical & Experimental Metastasis. 2010; 27: 251–259.
[35] Mali A V, Joshi A A, Hegde M V, Kadam S S. Enterolactone modulates the ERK/NF-κB/Snail signaling pathway in triple-negative breast cancer cell line MDA-MB-231 to revert the TGF-β-induced epithelial-mesenchymal transition[J]. Cancer biology & medicine, 2018, 15(2): 137-156.
[36] Li Q H, Liu Z Z, Ge Y, Liu X, Xie XD, Zheng ZD, et al. Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial-to-mesenchymal transition. Oncology Reports. 2020; 44: 509–518.
[37] Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100: 57–70.
[38] Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nature Reviews Molecular Cell Biology. 2014; 15: 49–63.
[39] Luciani D S, White S A, Widenmaier S B, Saran VV, Taghizadeh F, Hu X, et al. Bcl-2 and Bcl-xL suppress glucose signaling in pancreatic b-cells. Diabetes. 2013; 62: 170–82.
[40] Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer—expanded options, evolving needs. Nature Reviews Clinical Oncology. 2022; 19: 91–113.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Top