2. Academic Validation
  3. Poly-l-Lysine inhibits VEGF and c-Myc mediated tumor-angiogenesis and induces apoptosis in 2D and 3D tumor microenvironment of both MDA-MB-231 and B16F10 induced mice model

Poly-l-Lysine inhibits VEGF and c-Myc mediated tumor-angiogenesis and induces apoptosis in 2D and 3D tumor microenvironment of both MDA-MB-231 and B16F10 induced mice model

  • Int J Biol Macromol. 2021 Jul 31:183:528-548. doi: 10.1016/j.ijbiomac.2021.04.109.
Souvik Debnath 1,  Avinaba Mukherjee 2,  Dhananjoy Saha 3,  Jyotirmayee Dash 4,  Tapan Kumar Chatterjee 5
Affiliations

Affiliations

  • 1 Department of Basic Medical Sciences, Purdue University, 625 Harrison St, West Lafayette, IN-47907, USA; Division of Pharmacology Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Jadavpur-700032, India. Electronic address: souvik123456@gmail.com.
  • 2 Department of Zoology, Charuchandra College, University of Calcutta, Kolkata-700029, India.
  • 3 Deputy Director, Technical Education, West Bengal State Council & Technical Education, Bikas Bhavan, Saltlake, Kolkata, West Bengal, India.
  • 4 School of Chemical Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata-700032, India.
  • 5 Division of Pharmacology Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Jadavpur-700032, India; Department of Pharmaceutical Science and Technology, JIS University, Kolkata, India; and Former Professor, Division of Pharmacology, Department of Pharmaceutical Technology, Former Director, Clinical Research Centre, Jadavpur University, Kolkata, India. Electronic address: dr.tkchatterjee@jisuniversity.ac.in.
PMID: 33892042 DOI: 10.1016/j.ijbiomac.2021.04.109
Abstract

Cancer is a widespread disease that has shown promising mortality worldwide. Our previous study has been shown the efficacy of Poly-l-lysine (PLL) as a promising cytotoxic effect against Cancer cells. However, exact-mechanism of PLL in 3D physiological relevant tumor-microenvironment and against tumor-angiogenesis has never been analysed. In this study, we have investigated apoptotic efficacy of PLL, if any in opposition to proliferative aggressive Cancer cell MDA-MB-231 both 2D and-3D Cell Culture conditions. Furthermore, PLL was administered in B16F10 murine melanoma cells induced BALB/c mice model. The study has been designed through transcription and translation level of PLL-induced tumor-angiogenesis and apoptotic gene-expression modulation level and various relevant histological studies in comparison with untreated control. Studies have shown anti-proliferative and anti-tumor angiogenic efficacy of PLL better in in-vitro 3D tumor-microenvironment against MDA-MB-231 breast Cancer cells. Furthermore, in-vivo model, PLL was found to suppress tumorigenesis process at minimum dose. PLL found to induce Apoptosis through-upregulation of cytosolic-cytochrome-C, Caspase-3 and PARP activations when administered in B16F10 induced in-vivo tumor. In blocking proliferation and tumor-angiogenesis, PLL was found to be effective as it significantly downregulated activity of VEGF, VEGFR2/KDR/Flk-1, Ki-67 and c-Myc expression. As PLL blocked tumor progression and induced DNA-break, also upregulated apoptotic process and recovered tissue architecture as revealed from histological study in comparison with untreated control. Overall PLL was found to be a promising anti-tumor angiogenic and anti-proliferative drug that was effective both in in-vitro breast Cancer 3D tumor-microenvironment and in-vivo metastatic-mice-model.

Keywords

3D tumor-microenvironment; Apoptosis; Caspase-3; Poly-l-lysine (PLL); VEGF.

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