Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.08.27.502223

Anti-tumour efficacy of Musa paradisiaca flower extracts on DMBA induced Mammary carcinogenesis in female Wistar rats.

Abstract

BackgroundSeveral reports have shown the beneficial advantages of Musa paradisiaca in wound healing activities and other ailments. Previously, our in vitro studies validated the anti-cancer activities of Musa flower extracts and confirmed the potential. This thread has led to our current investigation to explore the anticancer potential in vivo. PurposeThis study focused on the efficacy of banana florets on DMBA induced breast cancer in female wistar rats. MethodsInduction of tumour using Dimethylbenzanthracene (DMBA) in female wistar rats. Hormonal, antioxidant and anticarcinogenic studies were performed in vivo. ResultsIn our current study, we investigated that tumour induction has an effect in disrupting the estrous cycle in mice which may result by hormonal fluctuation levels. Antioxidant and hormonal analysis in vivo revealed the imbalance in estrogen and progesterone levels in untreated group compared to the treated ones. Floral crude extract treatment in vivo has shrunken the tumour volume in flower extract treatment group as well as in standard drug compared to the control. Histopathological staining confirms the disruption of epithelial tissues in tumour induced groups compared to the treated ones. Moreover, Musa floral treatment has shown to revert the damaged tissue morphology in the treated groups compared to the saline treated one. In-vitro studies in MCF-7 and MDA-MB-231 breast cancer cell lines has shown the potent anti-tumorigenic activity using Musa floral extracts. ConclusionTaken together, our finding confirmed that banana flower extracts showcase anti-carcinogenic activity against breast cancer both in vitro and in vivo. Tumour induction in mice has an effect in showing the disruption of estrous cycles. HighlightsO_LIMusa paradisiaca crude ethanolic flower extracts have a potential in reducing the tumour growth. C_LIO_LIDMBA induced cancer has a deleterious effect on estrogen cycles in female wistar rats. C_LIO_LIDisruption of epithelial morphology was observed in tumour induced wistar rats. C_LIO_LITreatment with crude Musa flower extracts on cancer induced rats shows the reduced level of damage and oxidative stress compared to the no treatment group. C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lavudi, K., s, H., Kokkanti, R. R., GVS, H., Patnaik, S., Penchalaneni, J.. 2022-08-27. Anti-tumour efficacy of Musa paradisiaca flower extracts on DMBA induced Mammary carcinogenesis in female Wistar rats.. https://doi.org/10.1101/2022.08.27.502223

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Epigenetic progression of pancreatic cancer to aggressive subtypes involves alternate routes of lineage reprogramming in subtype-intermediate progenitor cells

Pancreatic ductal adenocarcinoma (PDAC) progression involves malignant cell state plasticity. Epigenetic changes underlie this plasticity, yet the PDAC cis-regulatory landscape remains understudied. To address this, we profiled 33 primary tumors and 7 metastases from 39 patients with single-cell ATAC-seq, paired with 10 single-cell RNA-seq profiles. We found that epigenetic GATA6+/KRT17+ co-accessibility identifies a classical-basal subtype-intermediate progenitor state (SIP) associated with better clinical outcomes. SIP cells display limited epigenetic reprogramming from premalignant epithelium and retain gastric-intestinal differentiation reminiscent of neoplastic precursors. Lineages without GATA6+/KRT17+ co-accessibility exhibit greater lineage and epithelial-mesenchymal plasticity. Classical PDACs that repress basal gene accessibility activate neural-like progenitor (NRP) and tuft lineage enhancers, whereas basal committed tumors display esophageal transdifferentiation. Compared to SIP, classical-NRP and basal committed tumors have poorer outcomes, and show distinct PD-1/PD-L1 immune proteomic phenotypes and prognostic myofibroblast epigenetic states, respectively. Our work reveals links between lineage reprogramming, EMT, and epigenetic progression in human PDAC.

cancer biology↗

Tissue resident CD4+ memory T-cells mark response to immune checkpoint inhibition in high-grade glioma

Background: Immune checkpoint inhibitors (ICI) are efficacious in many solid tumors, but response in glioma is restricted to a small subgroup. The determinants of response and resistance to ICI remain poorly understood. Methods: Here we exploit a syngeneic hypermutated high-grade glioma model with dichotomous response to combined PD-1 and CTLA-4 inhibition to unravel determinants of tumor-infiltrating T-cells driving response. Tumor-infiltrating T-cells from ICI-responsive and non-responsive tumors were analyzed by single-cell RNA and T-cell receptor sequencing and tumor-reactive T-cell receptor clonotypes were functionally validated to characterize their transcriptional phenotypes. We verify our findings in IDH1 wildtype glioblastoma patients treated with neoadjuvant pembrolizumab. Results: ICI response was associated with intratumoral clonal expansion of tumor-reactive cytotoxic T-cells and increased infiltration of CXCR6+ CD4+ tissue resident memory T-cells (Trm). CD4 stem-like memory T-cells in responding tumors demonstrated elevated interferon responses, following trajectories toward clonally expanded Trm, versus trajectories toward exhaustion in non-responsive tumors. In responsive tumors, CD4+ Trm interacted with infiltrating CXCR3+ tumor-reactive and clonally expanded, yet transcriptionally versatile cytotoxic T-cells. Probing the post neoadjuvant ICI high-grade glioma patient tissue dataset, we confirmed increased CXCR6 expression in CD4+ T cells and the association of CD4+ Trm with prolonged overall survival. Conclusion: These findings identify CD4 tissue-resident memory T-cells as determinants of ICI response in IDH1 wildtype high-grade glioma and warrant their further investigation to improve immunotherapy outcomes.

cancer biology↗

Low-dose doxorubicin drives caveolin-1 depended re-epithelialization of breast cancer cells as a mechanism of cancer plasticity

Breast cancer progression is driven by dynamic changes in epithelial plasticity, membrane organization, and intracellular signaling, yet the effects of sustained low-dose chemotherapy on these processes remain poorly understood. Here, we investigated the impact of prolonged low-dose doxorubicin on membrane remodeling, epithelial phenotype, membrane-associated Ras lipid-anchor localization, and autophagy in mesenchymal-like MDA-MB-231 breast cancer cells. Low-dose doxorubicin significantly increased Caveolin-1 expression and enhanced E-cadherin protein levels, accompanied by a transition toward a more compact epithelial-like morphology with increased cell-cell contacts. Live-cell imaging demonstrated a significant reduction in the membrane-to-cytoplasm fluorescence ratio of the lipid-anchored GFP-tH probe, indicating redistribution from the plasma membrane to the cytoplasm following treatment. Analysis of autophagy-related proteins revealed decreased LC3-I together with increased LC3-II, ATG5, and p62 expression, consistent with autophagosome accumulation and impaired autophagic flux. Collectively, our findings demonstrate that low-dose doxorubicin promotes extensive remodeling of plasma membrane organization, epithelial plasticity, membrane-associated lipid-anchor localization, and autophagy. This integrated response reveals previously unrecognized links between membrane architecture, Ras membrane association, and autophagy during phenotypic reprogramming of breast cancer cells, providing mechanistic insight into cellular adaptations elicited by sub-cytotoxic doxorubicin exposure.

cancer biology↗