scholarly journals Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tadanobu Shimura ◽  
Priyanka Sharma ◽  
Geeta G. Sharma ◽  
Jasjit K. Banwait ◽  
Ajay Goel

AbstractThe high degree of morbidity and mortality in colorectal cancer (CRC) patients is largely due to the development of chemoresistance against conventional chemotherapeutic drugs. In view of the accumulating evidence that various dietary botanicals offer a safe, inexpensive and multi-targeted treatment option, herein, we hypothesized that a combination of Andrographis paniculata and Oligomeric Proanthocyanidins (OPCs) might interact together with regard to anti-tumorigenic activity in CRC. As a result, we demonstrated the enhanced anti-cancer activity between these two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. Furthermore, we validated these findings in subcutaneous xenograft model and in patient derived primary epithelial 3D organoids. Transcriptomic profiling identified involvement of metabolic pathways and ferroptosis-associated genes, including HMOX1, GCLC and GCLM, that may be responsible for the increased anti-tumorigenic activity by the two compounds. Collectively, our study provides novel evidence in support of the combinatorial use of andrographis and OPCs as a potential therapeutic option, perhaps as an adjunctive treatment to classical drugs, in patients with colorectal cancer.

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Somrudee Reabroi ◽  
Rungnapha Saeeng ◽  
Nittaya Boonmuen ◽  
Teerapich Kasemsuk ◽  
Witchuda Saengsawang ◽  
...  

2015 ◽  
Vol 15 ◽  
pp. 264-273 ◽  
Author(s):  
Yuwen Ting ◽  
Yi-Shiou Chiou ◽  
Min-Hsiung Pan ◽  
Chi-Tang Ho ◽  
Qingrong Huang

Membranes ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 91
Author(s):  
Katia Cortese ◽  
Silvia Marconi ◽  
Cinzia Aiello ◽  
Maria Cristina Gagliani ◽  
Serena Pilato ◽  
...  

Colorectal cancer (CRC) is one of the main causes of cancer-related death in developed countries. Targeted therapies and conventional chemotherapeutics have been developed to help treat this type of aggressive cancer. Among these, the monoclonal antibodies cetuximab (Cxm) and panitumumab specifically target and inactivate the signaling of ERBB1 (EGF receptor), a key player in the development and progression of this cancer. Unfortunately, these antibodies are effective only on a small fraction of patients due to primary or secondary/acquired resistance. However, as ERBB1 cell surface expression is often maintained in resistant tumors, ERBB1 can be exploited as a target to deliver other drugs. Liposomes and immunoliposomes are under intensive investigation as pharmaceutical nanocarriers and can be functionalized with specific antibodies. In this study, we first investigated the anti-cancer activity of a cell permeable tripeptide, leucine-leucin-norleucinal (LLNle), an inhibitor of gamma-secretase and proteasome, in three different CRC cell lines that express ERBB1. We formulated LLNle-liposomes and Cxm-conjugated LLNle-loaded liposomes (LLNle-immunoliposomes) and evaluated their efficacy in inhibiting cell survival. Despite similar pro-apoptotic effects of free LLNle and LLNle-liposomes, immunoliposomes-LLNle were significantly less effective than their unconjugated counterparts. Indeed, immunoliposomes-LLNle were readily internalized and trafficked to lysosomes, where LLNle was likely trapped and/or inactivated. In conclusion, we demonstrated that LLNle was readily delivered to CRC cell lines by liposomes, but immunoliposomes-LLNle failed to show significant anti-cancer activity.


2014 ◽  
Vol 26 (02) ◽  
pp. 1450026 ◽  
Author(s):  
Juanjuan Li ◽  
Mei Yue ◽  
Xiaodong Shi ◽  
Shunqiao Feng ◽  
Ruihong Tang ◽  
...  

Objective: To investigate anti-cancer activity of the novel survivin siRNA Folate Receptor (FR)-targeted Polyethylene-Glycol Liposomes (PEG) liposomes in K562-bearing nude mice. Methods: The leukemia cell line K562 xenograft model was established in balb/c nu/nu mice, and survivin siRNA FR-targeted PEG liposomes was administrated by intraperitoneal (i.p.). The same volume of liposomes was administrated as placebo control. The real time PCR and western blotting were used to examine the knocking down effect. The tumor weight and size in nude mice was measured to evaluate the inhibitory effect in vivo. Results: The expression ratio of survivin mRNA in siRNA group was 0.35 ± 0.1 (survivin/GAPDH) vs. 1.85 ± 0.65 in control group with significant difference (p < 0.05), as well as protein level by western blotting analysis (p < 0.05). The results also showed the novel survivin siRNA liposomes could inhibit the growth of K562 in xenograft model. Conclusion: This novel survivin siRNA FR-targeted PEG liposome delivery system may be a potential gene therapy for the treatment of leukemia.


2021 ◽  
Author(s):  
Sophie Mockly ◽  
Élisabeth Houbron ◽  
Hervé Seitz

The miR-34a microRNA (miRNA) is currently thought to act as a tumor suppressor: its locus is frequently deleted in human tumors and it is believed to repress cell proliferation. We re-visited the evidence of its anti-cancer activity. Our results show that miR-34a is not generally down-regulated in primary tumors relatively to normal adjacent tissues, and the occasional deletion of miR-34a in human cancers is not due to an anti-tumorigenic activity of that gene, but rather, to its genomic proximity with an actual tumor suppressor. Its anti-proliferative action was observed upon large, supra-physiological transfection of synthetic miR-34a in cultured cells, and our data indicates that endogenous miR-34a levels do not have such an effect. We thus conclude that the generally accepted tumor-suppressive function of miR-34a is erroneous.


2021 ◽  
Author(s):  
Syeda Kiran Shahzadi ◽  
Noushad Karuvantevida ◽  
Yajnavalka Banerjee

BACKGROUND Cancer is the third leading cause of death in the United Arab Emirates (UAE) after cardiovascular diseases and accidents. In UAE, colorectal cancer (CRC) is the first and fourth most common cancer in males and females respectively. Several treatment modalities have been employed for cancer treatment such as surgery, radiotherapy, chemotherapy, hormone replacement therapy, and immunotherapy. These treatment modalities often elicit adverse effects on normal cells, causing toxic side effects. To circumvent these toxicities, there has been an increased impetus towards the identification of alternate treatment strategies. Animal venoms are veritable gold mines of pharmacologically active polypeptides and proteins. OBJECTIVE In this proof-of-concept study, we avail a high throughput “Venomics” strategy to identify and characterize anticancer bioactive peptides (BAP) from 20 different animal venoms specifically targeting CRC. We chose to focus on CRC as it is one of the foremost health issues in the UAE. METHODS In initial study, we will screen 2500 different peptides derived from 20 different animal venoms for anticancer activity specifically directed against three CRC cell lines and two control cell lines employing the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay for cytotoxicity. Three venoms of the 20, which exhibited specific and potent anticancer activity directed against the three CRC cell lines will be selected; and from these three venoms the specific peptide(s) with anti-CRC activity will be isolated and characterized. RESULTS This study is at the protocol development stage only, and as such, no results are available. CONCLUSIONS In summary, the proposed study will not only generate therapeutic leads to manage/treat one of the leading health issues in the UAE i.e., CRC, but is also of commercial interest as the identified BAP with specific anti-cancer activity against CRC can be patented for commercialization.


Author(s):  
Ramachandran K ◽  
Venketnarayanan R ◽  
Rajesh Yadav ◽  
Suresh R ◽  
Sumitra Devkota

Colorectal cancer is the second leading cause of cancer death in the United States for both men and women. The rate of colon cancer incidence was low in India but is presently increasing; out of 3.5 million cancer cases, 35,000 have colon cancer. Polyps which are the small growths in the colon are most often benign, even though some have the potentiality to become cancerous. Up to two-thirds of the colorectal polyps are pre-malignant and they are linked with a risk of colorectal cancer. About 60% of currently used anti-cancer agents are derived from a natural source (i.e. plants). In our study anti-cancer potential of the extract of Coldenia procumbens was studied and the synthesis of the anti-cancer moiety has been done. With the findings, it can be concluded that the plant Coldenia procumbens Linn and possess anti colorectal cancer activity. Before the clinical usage of extract, through toxicological profile has to be determined on the crude extracts as well as on isolated compounds to confirm the safety of the drug.


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