Influences of aqua-(2-formylbenzoato) triphenyltin(IV) on regression of hypoxic solid tumor through mitochondrial mediated pathway by inhibiting Hif-1 alpha.

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Tác giả: Tushar S Basu Baul, Pooja Goswami, Biplob Koch, Abhijit Mandal, Partha Pratim Manna, Arvind Kumar Singh, Ranjeet Singh, Virendra Singh

Ngôn ngữ: eng

Ký hiệu phân loại: 959.3034 *Thailand

Thông tin xuất bản: England : Scientific reports , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 66738

Tumor hypoxia is the major hindrance behind cancer chemotherapy and the foremost reason for the less effectiveness of most anticancer drugs. We herein inquire into the mechanistic part and therapeutic efficacy of our previously reported compound, aqua-(2-formylbenzoato) triphenyltin (IV) (abbreviated as OTC), in a hypoxic solid tumor-bearing mouse model (BALB/c). In addition to solid tumors, we investigated the therapeutic potential of OTC in intraperitoneal tumor and in in vitro system. Following treatment, mitochondrial dynamics, tumor load regression, survival analysis and histopathological parameters were analyzed. Furthermore, the differential expression levels of cleaved PARP-1, Hif-1α, VEGF and apoptotic genes such as Bax, Bcl-2, p53, and caspase 3 at the mRNA and protein levels were assessed. Our findings demonstrate that OTC significantly induces tumor regression and increased survivability by down regulating the expression of the hypoxia-associated genes Hif-1α and VEGF while elevating the levels of cleaved PARP-1 and p53. In contrast, the commercially available drug doxorubicin was found less effective and failed to respond in the tumor microenvironment. Furthermore, increased mitochondrial aggregation and membrane permeability and activation of Bax, caspase 3 and caspase-9 and release of Cytochrome-c from the mitochondrial membrane at RNA level confirms the mitochondrial pathway of apoptosis. Therefore, our present findings reveal that newly synthesized OTC potentially induces apoptosis and could be a promising compound against the tumor microenvironment.
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