42^nd World Cancer Conference

Biography

Biography: Gacche Raju

Abstract

Statement of the Problem: Triple-negative breast cancer (TNBC) is a heterogeneous group of breast carcinomas distinguished by rapid metastatic growth and aggressive tumor invasion ability, leading to high female mortality. On the eve of emerging drug resistance, there is a need to identify candidate drugs that will improve the efficacy of conventional therapeutic regimes. The purpose of this study was to investigate the effect of dietary flavonoids on regulation of epigenetic markers and miRNAs involved in progression of TNBC.

Methodology & Theoretical Orientation: Series of in vitro cell culture assays such as MTT assay for cell viability, cell migration assay, ROS assay, cell cycle inhibition and apoptosis assay was carried out FACs analysis. The gene expression profile of HDAC 1-11 isomers, DNMT-1/3 and HMT, Onco- and tumor suppressor miRNAs and MRP1 & BCRP was determined using RT-qPCR. The protein expression analysis of HDACs 1, 3, 4 & 6 and apoptosis marker proteins was analyzed using immunoblotting.  

Findings: The Apigenin, Galangin and luteolin, showed good potential to modulate the expression profiles of epigenetic regulators in TNBC (MD-MB-231) cells. The HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6 and HDAC8 were downregulated in MD-MB-231 cells after treatment with dietary flavonoids such as Apigenin, Galangin and Luteolin. The results were normalized with GAPDH. The protein expression level of HDAC1, HDAC3, HDAC4 and HDAC6 were reduced after the treatment of Apigenin, Galangin and Luteolin. The expression of DNMT1 and HMT downregulated after the treatment of Apigenin, Galangin and Luteolin. The oncomiR-21 was downregulated after the treatment of Apigenin and Luteolin. Whereas, the tumor suppressor miRNAs such as miR34 and miR200b was significantly upregulated after the treatment of Apigenin, Galangin and Luteolin. The combinatorial studies suggested the synergistic effect (CI<1) between flavonoids and SAHA against MDA-MB-231 cells. The qRT-PCR and Western analysis results were supported by molecular docking and MD simulation studies.

Conclusion & Significance: On the eve of evolving drug resistance, tumor heterogeneity, and off target toxicities there is need to find alternative candidate adjuvant therapeutic molecules which will augment the efficacy of conventional drugs and circumvent the drug resistance. The results of the present study clearly indicate the significance of lead flavonoid molecules as adjuvant drug molecules for effective treatment of TNBC.     

Recent Publications:

1. Choudhari J, Nimma R, Nimal SK, Totakura Venkata SK, Kundu GC, Gacche RN. (2023) Prosopis juliflora (Sw.) DC phytochemicals induce apoptosis and inhibit cell proliferation signaling pathways, EMT, migration, invasion, angiogenesis and stem cell markers in melanoma cell lines. J Ethnopharmacol. 10; 312:116472. (IF 5.2).
2. Pote MS, Gacche RN. (2023). ATP-binding cassette efflux transporters and MDR in cancer. Drug Discov Today. 2023 Feb 16:103537. doi: 10.1016/j.drudis.2023.103537. (IF 8.4).
3. Deepshikha Singh, Yehuda G. Assaraf, Rajesh N. Gacche (2022). Long Non-coding RNA Mediated Drug Resistance in Breast Cancer. Drug Resistance Updates. 100851, https://doi.org/10.1016/j.drup.2022.10085. (IF 22.84).
4. Sonali S. Kamble, Kapil K. Patil, Shrikant V. Hese, Bhaskar S. Dawane, Choudhari Jasoda, Kumar TVS, Rajesh N. Gacche (2022). “Chloroxylon swietenia (Roxb.) DC induces cell death & apoptosis by down-regulating the NF-κB pathway in MCF-7 breast cancer cells: in vitro and in vivo investigations” Cancer Reports e1600.
5. Navanath Kumbhar, Snehal Nimal, Sagar Barale, Subodh Kamble, Rohit Bavi, Kailas Sonawane, Rajesh Gacche (2022). Identification of novel leads as potent inhibitors of HDAC3 using ligand-based pharmacophore modeling and MD simulation. Scientific Reports 12(1):1712 (Nature Publication).