Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

Abstract

Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death. For example, T24 cells were treated with 12 µM CBD for 48 h, flow cytometry analysis demonstrated that early and late apoptotic cells were accounted for by 49.91%, indicating CBD enhanced cell apoptosis ability. To deeper explore molecular mechanisms, the CBD-treated T24 cell transcriptome libraries were established. KEGG analysis implied that the significantly changed genes were enriched in the PI3K/Akt pathway. qRT-PCR and Western blot assays verified that CBD regulated BC cells growth and migration and induced apoptosis by inactivating the PI3K/Akt pathway. Meanwhile, the developed chitosan to wrap CBD-loaded PLGA nanoparticles can significantly enhance the adhesion of the material to the mouse bladder wall, and the binding efficiency of mucin to chitosan-PLGA nanoparticles reached 97.04% ± 1.90%. In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.

Anti-cancer properties of cannflavin A and potential synergistic effects with gemcitabine, cisplatin, and cannabinoids in bladder cancer

“…In bladder cancer, the effects of cannabis or compounds isolated from cannabis have not been extensively studied. A study recently demonstrated that the combination of Δ 9 -tetrahydrocannabinol and cannabichromene produced synergistic effects in a bladder cancer model (Anis et al 2021), while another focused on the effects of cannabidiol and their potential formulation within nanoparticles to treat bladder cancer (Chen et al 2021). Here, we show that other compounds from cannabis, like cannflavin A, may also induce beneficial cytotoxic and synergistic effects on bladder cancer cells.…”

“…Our results showed that while some synergy is possible with gemcitabine or cisplatin, much higher levels of synergy occurred when cannabinoids like Δ 9tetrahydrocannabinol, cannabichromene, or cannabivarin are combined with cannflavin A. In recent years, several groups have begun exploring the potential of cannabinoids as anticancer agents, and this in various cancer types (Blasco-Benito et al 2018;López-Valero et al 2018a, b), including bladder cancer (Anis et al 2021;Chen et al 2021).…”

“…Another study showed that cannabidiol (CBD) effectively inhibited growth and migration and induced apoptosis by inactivating the PI3K/AKT pathway in bladder cancer cell lines. The authors also showed that various CBD-loaded nanoparticles had the potential to significantly enhance the adhesion of CBD in the bladder wall and reduce potential damage caused by repeated perfusions and therefore improve long-term treatment (Chen et al 2021). Our group also observed that cannabinoids can produce synergistic cytotoxic effects with gemcitabine and/or cisplatin in bladder cancer cell lines.…”

(Nano)platforms in bladder cancer therapy: Challenges and opportunities

“… 79 The studies highlight the fact that delivery of phytochemicals with nanostructures is of importance in increasing their capacity for cell death induction and this is favorable for bladder cancer therapy (Figure 1 ). 80 , 81 , 82 However, more studies regarding molecular pathways affected by phytochemical‐loaded nanostructures, their internalization route, and development of smart and other kinds of nanoparticles are vital. The advantages related to nanostructures are the evaluation of particle size, zeta potential, and encapsulation efficiency after the loading of chemotherapeutic agent.…”

The Establishment of Quantitatively Regulating Expression Cassette with sgRNA Targeting BIRC5 to Elucidate the Synergistic Pathway of Survivin with P-Glycoprotein in Cancer Multi-Drug Resistance

“…Survivin Might Mediate Tumor Cell's MDR via the PI3K/Akt/mTOR Pathway PI3K/Akt/mTOR signaling pathway was necessary for tumor cells' survival (Khan et al, 2013;Riquelme et al, 2016;Chen et al, 2018;Liu et al, 2020;Chen et al, 2021) (e.g., breast cancer (Yin et al, 2017;Nunnery and Mayer, 2020), head and neck cancer (Marquard and Jücker, 2020), and lung cancer (Tan, 2020)). This pathway also played an essential role in promoting cell growth, proliferation, metastasis, and chemotherapy resistance (Khan et al, 2013;Ahmad et al, 2020;Liu et al, 2020).…”