Presenting Author

Ankit Srivastava

Presentation Type

Oral Presentation

Discipline Track

Biomedical Science

Abstract Type

Research/Clinical

Abstract

Background: Breast cancer has become the most frequent tumor worldwide and is expected to have a large impact on cancer fatalities globally. Thus, the development of precise molecular diagnosis and prognosis is essential for the effective treatment of breast cancer patients. Doxorubicin (DOXO) is the widely accepted chemotherapeutic drug for the treatment of breast cancer. However, the primary challenge with current chemotherapy drugs is their toxic effects on healthy tissues. Moringin (MG), an Isothiocyanate (ITC) is produced from the seeds of Moringa oleifera. It is produced from the myrosinase-catalyzed hydrolysis of glucomoringin. Chemosensitization is a strategy used in cancer treatment to make cancerous cells more responsive to chemotherapeutic drugs. A chemosensitizing drug is used in therapy to reduce the doses of potential anticancer drugs, tackle the resistance of cancer cells to these treatments, prevent healthy cells from toxicity, and decrease side effects for patients. In this study, we investigated the potential of MG alone and in conjunction with DOXO against breast cancer cells.

Methods: MCF-7 and MDA-MB-231 breast cancer cell lines were used in the investigation. The chemo-sensitization experiments of MG, both alone and in combination with DOXO, were investigated by using the MTT and colony formation assay. Apoptosis was examined by using the AO/PI dual staining, cell cycle analysis, and mitochondrial membrane potential measurement. Expression of cell survival proteins was assessed through semi-quantitative PCR and western blotting. Expression of long non-coding RNAs was performed by qRT-PCR.

Results: The MTT and clonogenic assay results revealed the anti-proliferative potential of MG both alone and in combination of DOXO. The expression of proteins involved in cell survival (PARP, Bcl-2, Bcl-xL and Survivin) is also downregulated in combination compared to individual drug. We observed an increase in the sub-G1 and S-phase population in MG and DOXO (both individual as well in combination). However, the G1 and G2/M population was slightly decreased with MG and DOXO (both individual as well in combination). The expression of oncogenic lncRNAs such as H19, HOTAIR and NKILA, were reduced and the expression of tumor suppressor genes such as MEG3, GAS5 and MALAT1 was increased.

Conclusions: Taken together, results of this study provide evidence that, MG in breast cancer cell lines increases the susceptibility of breast cancer cells to DOXO.

Academic/Professional Position

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Moringin, an isothiocyanate improves the susceptibility of breast cancer cells to doxorubicin

Background: Breast cancer has become the most frequent tumor worldwide and is expected to have a large impact on cancer fatalities globally. Thus, the development of precise molecular diagnosis and prognosis is essential for the effective treatment of breast cancer patients. Doxorubicin (DOXO) is the widely accepted chemotherapeutic drug for the treatment of breast cancer. However, the primary challenge with current chemotherapy drugs is their toxic effects on healthy tissues. Moringin (MG), an Isothiocyanate (ITC) is produced from the seeds of Moringa oleifera. It is produced from the myrosinase-catalyzed hydrolysis of glucomoringin. Chemosensitization is a strategy used in cancer treatment to make cancerous cells more responsive to chemotherapeutic drugs. A chemosensitizing drug is used in therapy to reduce the doses of potential anticancer drugs, tackle the resistance of cancer cells to these treatments, prevent healthy cells from toxicity, and decrease side effects for patients. In this study, we investigated the potential of MG alone and in conjunction with DOXO against breast cancer cells.

Methods: MCF-7 and MDA-MB-231 breast cancer cell lines were used in the investigation. The chemo-sensitization experiments of MG, both alone and in combination with DOXO, were investigated by using the MTT and colony formation assay. Apoptosis was examined by using the AO/PI dual staining, cell cycle analysis, and mitochondrial membrane potential measurement. Expression of cell survival proteins was assessed through semi-quantitative PCR and western blotting. Expression of long non-coding RNAs was performed by qRT-PCR.

Results: The MTT and clonogenic assay results revealed the anti-proliferative potential of MG both alone and in combination of DOXO. The expression of proteins involved in cell survival (PARP, Bcl-2, Bcl-xL and Survivin) is also downregulated in combination compared to individual drug. We observed an increase in the sub-G1 and S-phase population in MG and DOXO (both individual as well in combination). However, the G1 and G2/M population was slightly decreased with MG and DOXO (both individual as well in combination). The expression of oncogenic lncRNAs such as H19, HOTAIR and NKILA, were reduced and the expression of tumor suppressor genes such as MEG3, GAS5 and MALAT1 was increased.

Conclusions: Taken together, results of this study provide evidence that, MG in breast cancer cell lines increases the susceptibility of breast cancer cells to DOXO.

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