Smoke rises after airstrikes on Aleppo's Castello road on June 2. (Abdalrhman Ismail/Reuters)

Rebel-held neighborhoods in the Syrian city of Aleppo have endured food shortages and devastating attacks throughout the civil war. Now pro-government forces have cut off the only road into those areas, leaving an estimated 300,000 people at risk of starvation.

U.N. officials and aid workers warn of deteriorated conditions in the divided city’s opposition districts. Residents there say that food prices have doubled and that hours-long power blackouts have worsened as fuel for generators runs out.

“We’re not starving yet, but we’re all panicking now,” said Maher Abu al-Walid, 25, who lives in a rebel area. He expressed concern about diminishing supplies of fruits, vegetables and milk for his wife and their 7-month-old daughter, Sham.

On July 7, Syrian President Bashar al-Assad’s army and allied militiamen from Lebanon and Iran seized parts of al-Mallah Farms, an elevated area in a northern neighborhood. That allowed them to use artillery and rockets to stop the use of nearby Castello Road, the last remaining route for supplies and weapons into rebel areas in the city’s east.

This week, pro-government forces managed to place checkpoints on the road, further cementing their control over it.

Severing those neighborhoods from other opposition strongholds in the country threatens to deal a blow to the rebellion and its main outside supporters, Turkey and Saudi Arabia, which supply Assad’s opponents with money and weapons. That scenario also signals another significant setback for U.S. policy in Syria, which backs the moderate opposition to Assad’s government and formally calls for his departure as part of a transition to end the conflict.

Residents trapped inside the opposition areas could face even more horrific conditions. The government is already besieging hundreds of thousands of Syrians in multiple areas across Syria, and dozens of people have died from starvation and lack of medical care, according to U.N. officials and aid workers. Opposition forces have also besieged a handful of government areas.

This is “a massive tragedy in the making,” said Emile Hokayem, a Middle East analyst at the London-based International Institute for Strategic Studies.

In an interview with NBC News, the Syrian leader denied that his forces are imposing sieges. “How do we prevent them from having food and we don’t prevent them from having armaments to kill us? What is the logic in this?” he said in the interview.

Control over all of Aleppo would nevertheless amount to a prize for Assad. Before the civil war reduced much of it to smolder and rubble, Aleppo was Syria’s largest city — home to 2 million people — and a major industrial and trading hub.

Rebels invaded the city in 2012, dividing it between opposition areas in the east and government-controlled ones in the west. Back then, many expected opposition forces to capture the entire city and eventually overthrow Assad.

Syrians line up to buy bread in a rebel-held neighborhood in Aleppo, Syira, on July 12. (Karam Al-Masri/AFP/Getty Images)

But this past February, pro-government militants backed by Russian warplanes nearly surrounded rebel neighborhoods and severed another key supply route leading northward to the Turkish border. That left Castello Road as the sole channel to Aleppo’s rebels.

Moscow, a key ally of the Syrian leader, helped turn the tide in Assad’s favor after intervening late last year.

Rebel fighters have intensified attacks since the Castello Road closure, firing intense artillery and rocket barrages in densely populated areas of government-controlled Aleppo. Those assaults have killed dozens of people, according to reports in Syrian state media.

Even though government-held districts have fared better relative to other areas of city, conditions have deteriorated. Rebel fighters and militants linked with Syria’s al-Qaeda affiliate, Jabhat al-Nusra, indiscriminately shell government areas, causing many casualties.

Opposition forces have vowed to form a united front to prevent a prolonged siege.

They have stopped government forces from establishing checkpoints along Castello Road, which runs west to the rebel-held Idlib province, bordering Turkey.

“We are doing all that we can to open Castello or find a new way to reach the city. We must do this,” said Adeeb Alsen, a member of the Jabhat Shamiya force that is part of the umbrella Free Syrian Army rebel coalition.

The rebels say that pro-government forces are bombing anything that moves on the road, named after an area restaurant and wedding hall that was popular before the conflict. It’s so dangerous, they say, that they can’t even retrieve bodies from bombed-out buses and passenger vehicles there.

“The situation is not good,” Capt. Hassan Haj Ali, a leader of the Suqour al-Jabal rebel group.

Residents in the city’s eastern areas say markets have shuttered since the road’s closure, and people are hoarding food and goods. Streets are emptier because of a lack of gasoline, said Abu Hamza, 35, a father of three who lives in Aleppo’s Fardos area.

“We started reducing the amount of food we eat and the number of meals we eat per day because we have to adapt to the new situation. This siege might last for a long time,” said Abu Hamza, a nickname.

Tens of thousands of people in Aleppo’s opposition areas rely on food and medical aid provided by outside donors. Complicating problems is the immense devastation already inflicted on the city’s civilian infrastructure, such as hospitals, which have been ravaged by Assad’s warplanes.

“It’s difficult, if not impossible, to resupply the city, and it’s difficult, if not impossible, for people to leave the city,” said Dominic Graham, the Syria-response coordinator for Mercy Corps. He was referring to rebel-held areas.

Residents say that charities and aid groups have stored supplies of food in case of a siege. Even so, people in the area accuse shop owners of attempting to profit from worsening shortages caused by the road closure.

“A lot of the groceries are closing, and the ones that are still open have no items for sale,” said Ameen Alhalabi, a resident in Aleppo who supports opposition forces. “We all know they’re hiding their food and goods so that they can sell them later at a higher price.”

He added, “The situation was already so bad, and now this?”

Zakaria Zakaria in Istanbul and Suzan Haidamous in Beirut contributed to this report.